Impact of human CD95 mutations on cell death and autoimmunity: a model

CD95/Fas/APO-1 can trigger apoptotic as well as nonapoptotic pathways in immune cells. CD95 signaling in humans can be inhibited by several mechanisms, including mutations in the gene encoding CD95. CD95 mutations lead to autoimmune disorders, such as autoimmune lymphoproliferative syndrome (ALPS)....

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Bibliographic Details
Published in:Trends in immunology 2022-01, Vol.43 (1), p.22-40
Main Authors: Seyrek, Kamil, Ivanisenko, Nikita V., Wohlfromm, Fabian, Espe, Johannes, Lavrik, Inna N.
Format: Article
Language:English
Subjects:
3D structure
ALPS
Amino acids
APO-1 protein
Apoptosis
Apoptosis - genetics
autoimmune disease
Autoimmune diseases
Autoimmune Diseases - genetics
Autoimmunity
Autoimmunity - genetics
CD95
CD95 antigen
Cell death
Cell Death - genetics
Fas antigen
fas Receptor - genetics
fas Receptor - metabolism
Humans
Immune system
Lymphocytes
Lymphoma
Lymphoproliferative Disorders - genetics
Mutation
Mutation - genetics
Proteins
Signal transduction
T cell receptors
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Summary:CD95/Fas/APO-1 can trigger apoptotic as well as nonapoptotic pathways in immune cells. CD95 signaling in humans can be inhibited by several mechanisms, including mutations in the gene encoding CD95. CD95 mutations lead to autoimmune disorders, such as autoimmune lymphoproliferative syndrome (ALPS). Gaining further insight into the reported mutations of CD95 and resulting alterations of its signaling networks may provide further understanding of their presumed role in certain autoimmune diseases. For illustrative purposes and to better understand the potential outcomes of CD95 mutations, here we assign their positions to the recently determined 3D structures of human CD95. Based on this, we make certain predictions and speculate on the putative role of CD95 mutation defects in CD95-mediated signaling for certain autoimmune diseases. CD95/Fas controls multiple cellular programs in immune cells by triggering apoptotic as well as nonapoptotic pathways.CD95 mutations can lead to immune system defects and certain autoimmune diseases.Mutations in different domains of CD95 affect all stages of CD95 signaling, from CD95L binding to assembly of the receptor complex.Recently resolved 3D crystal structures of human CD95 provide remarkable insights into the presumed effects of mutations on altered CD95-mediated signaling in certain autoimmune diseases.
ISSN:1471-4906
1471-4981
DOI:10.1016/j.it.2021.11.006